D Basile1, C Broudin2, J F Emile3, A Falcoz4, F Pagès5, L Mineur6, J Bennouna7, C Louvet8, P Artru9, S Fratte10, F Ghiringhelli11, T André12, V Derangère13, D Vernerey4, J Taieb14, M Svrcek15. 1. Department of Hepatogastroenterology and Gastrointestinal Oncology, University of Paris (Paris Descartes), SIRIC CARPEM, Georges Pompidou European Hospital, AP-HP, Paris, France; Department of Medicine, DAME, University Hospital of Udine, Udine, Italy; Department of Medical Oncology, ULSS8 Berica, Vicenza, Italy. 2. Department of Pathology, Georges Pompidou European Hospital, AP-HP, Paris, France. 3. Department of Pathology, Ambroise Paré Hospital, AP-HP, Boulogne, France; SIRIC CARPEM, University of Paris, Paris, France; Research Unit EA4340 'Biomarkers and Clinical Trials in Oncology and Onco-Hematology', Versailles Saint-Quentin-en-Yvelines University, Boulogne, France. 4. Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon, Besançon, France; INSERM UMR1098, University of Bourgogne Franche-Comté, National Institute of Health and Research, Etablissement Français du Sang Bourgogne Franche-Comté, Besançon, France. 5. Department of Immunology, AP-HP, Hôpital Européen Georges Pompidou, University of Paris, Paris, France. 6. Department of Radiation Therapy, Institut Sainte Catherine, Avignon, France. 7. Department of Medical Oncology, University Hospital of Nantes, Nantes, France. 8. Department of Medical Oncology, Institut Mutualiste Montsouris, Paris, France. 9. Department of Medical Oncology, Jean Mermoz Private Hospital, Lyon, France. 10. Department of Medical Oncology, Belfort-Montbeliard Hospital, Montbeliard, France; Besançon Hospital, Besançon, France. 11. Platform of Transfer in Cancer Biology, Centre Georges François Leclerc, INSERM LNC UMR1231, University of Bourgogne Franche-Comté, Dijon, France. 12. Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, Paris, France; SIRIC CURAMUS, Sorbonne University, Paris, France. 13. Besançon Hospital, Besançon, France; Platform of Transfer in Cancer Biology, Centre Georges François Leclerc, INSERM LNC UMR1231, University of Bourgogne Franche-Comté, Dijon, France. 14. Department of Hepatogastroenterology and Gastrointestinal Oncology, University of Paris (Paris Descartes), SIRIC CARPEM, Georges Pompidou European Hospital, AP-HP, Paris, France. Electronic address: jtaieb75@gmail.com. 15. Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, Paris, France; SIRIC CURAMUS, Sorbonne University, Paris, France. Electronic address: magali.svrcek@aphp.fr.
Abstract
BACKGROUND: Histological characteristics at the invasive front may reflect tumor aggressiveness; specifically, tumor budding (Bd) is an emerging prognostic biomarker in colon cancer (CC). We explored further the significance of Bd for risk stratification by evaluating survival of stage III CC patients included in the IDEA-France phase III trial. PATIENTS AND METHODS: This post-hoc study was conducted on tissue slides from 1048 stage III CC patients. Bd was scored by central review by the Bd criteria of the 2016 International Tumor Budding Consensus Conference (ITBCC 2016) and classified as Bd1 (0-4 buds/0.785 mm2), Bd2 (5-9 buds), and Bd3 (≥10 buds) categories. Disease-free survival (DFS) and overall survival (OS) were analyzed by the log-rank test. Clinicopathological features and Immunoscore® were correlated with Bd. RESULTS: Overall, Bd1, Bd2, and Bd3 were observed in 39%, 28%, and 33% of CC, respectively. Bd2 and Bd3 were associated with vascular (P = 0.002) and perineural invasions (P = 0.0009). The 3-year DFS and the 5-year OS rates for Bd (1 versus 2-3) were 79.4% versus 67.2% (P = 0.001) and 89.2% versus 80.8% (P = 0.001), respectively. This was confirmed after adjustment for relevant clinicopathological features for DFS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.12-1.77, P = 0.003] and OS (HR 1.65, 95% CI 1.22-2.22, P = 0.001). When combined with pTN stage and Immunoscore® subgroups, Bd significantly improved disease prognostication. CONCLUSIONS: Bd demonstrated its independent prognostic value for DFS and OS. Given these findings, Bd as per the ITBCC 2016 should be mandatory in every pathology report in stage III CC patients. Bd and Immunoscore® could play a complementary role in personalized health care in this setting.
BACKGROUND: Histological characteristics at the invasive front may reflect tumor aggressiveness; specifically, tumor budding (Bd) is an emerging prognostic biomarker in colon cancer (CC). We explored further the significance of Bd for risk stratification by evaluating survival of stage III CC patients included in the IDEA-France phase III trial. PATIENTS AND METHODS: This post-hoc study was conducted on tissue slides from 1048 stage III CC patients. Bd was scored by central review by the Bd criteria of the 2016 International Tumor Budding Consensus Conference (ITBCC 2016) and classified as Bd1 (0-4 buds/0.785 mm2), Bd2 (5-9 buds), and Bd3 (≥10 buds) categories. Disease-free survival (DFS) and overall survival (OS) were analyzed by the log-rank test. Clinicopathological features and Immunoscore® were correlated with Bd. RESULTS: Overall, Bd1, Bd2, and Bd3 were observed in 39%, 28%, and 33% of CC, respectively. Bd2 and Bd3 were associated with vascular (P = 0.002) and perineural invasions (P = 0.0009). The 3-year DFS and the 5-year OS rates for Bd (1 versus 2-3) were 79.4% versus 67.2% (P = 0.001) and 89.2% versus 80.8% (P = 0.001), respectively. This was confirmed after adjustment for relevant clinicopathological features for DFS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.12-1.77, P = 0.003] and OS (HR 1.65, 95% CI 1.22-2.22, P = 0.001). When combined with pTN stage and Immunoscore® subgroups, Bd significantly improved disease prognostication. CONCLUSIONS: Bd demonstrated its independent prognostic value for DFS and OS. Given these findings, Bd as per the ITBCC 2016 should be mandatory in every pathology report in stage III CC patients. Bd and Immunoscore® could play a complementary role in personalized health care in this setting.